The objectives of the Center of Biomedical Research Excellence in Women's Health (COBREWH) are to deepen our understanding of the unique role of gender, female reproductive hormones, and selective estrogen modulators (SERMs) in the manifestation of health and disease and use this focus as a platform to develop promising junior investigators and enhance their success at competing for NIH grant support. We will achieve these objectives by (1) assembling a cadre of established NIH- funded scientists to examine timely and important questions related to gender, female reproductive hormones and hormone action, (2) mentoring junior faculty with state-of-the-art multi-disciplinary training in concepts relevant to women's health, (3) mentoring junior faculty in research projects focused on women's health that will insure that they successfully establish independent NIH-funded research careers, (4) developing and supporting shared core facilities to optimize use by COBREWH faculty in cutting edge methods, (5) facilitating pilot projects and collaborations in complementary research areas that are essential to improving women's health, and (6) strategically hiring promising new faculty to develop a critical mass of funded, productive and well-respected investigators in women's health research. A critical challenge for the COBREWH is to provide junior investigators with focused in-depth research experiences that enhance their chances to obtain funding in a highly competitive funding environment, while providing the inter-disciplinary framework within which they can grow and thrive over the long-term. To meet this challenge we have divided the research in this COBREWH into 3 broad overlapping themes which will umbrella 5 research projects that interact with each other in terms of concepts and methods. These research projects are included in the COBREWH because they attack critical questions in women's health and because the University of Kentucky is fortunate to have senior, well-funded faculty with extensive experience in mentoring junior investigators in each of these areas. Thus, junior investigators will learn from established NIH-funded faculty who utilize a broad spectrum of state-of-the-art integrative, clinical, cellular and molecular approaches to probe critical questions in women's health research. This structure will insure that the proposed COBREWH program will meet the challenge of exponentially increasing the NIH- funded research in the Commonwealth of Kentucky.